doi: 10.1161/hy0202.104142
(Hypertension. 2002;39:239.)
© 2002 American Heart Association, Inc.
Scientific Contributions |
Increased Dietary Salt Activates Rat Aortic Endothelium
From the Nephrology Research and Training Center, Comprehensive Cancer Center, and Cell Adhesion and Matrix Research Center, Division of Nephrology, Department of Medicine, and Department of Physiology and Biophysics, University of Alabama at Birmingham; and the Department of Veterans Affairs Medical Center, Birmingham, Alabama.
Correspondence to Paul W. Sanders, MD, Division of Nephrology/Department of Medicine, 642 Lyons-Harrison Research Building, 701 South 19th Street, University of Alabama at Birmingham, Birmingham, AL 35294-0007. E-mail psanders{at}uab.edu
The function of vascular endothelium as a biomechanical sensor permits alterations in gene expression in the vascular tree in response to wall stress. The present study explored the mechanism by which the arterial endothelium responds to changes in dietary salt. Normotensive rats were fed diets containing varying amounts of NaCl for 4 days. At that time, levels of phosphorylated p38 MAP kinase, p42/44 MAP kinase, and p46/54 JNK/SAP kinase increased when the diet contained 
3.0% NaCl. Kinase assays demonstrated dose-response relationships between dietary salt intake and the activities of p38 MAP kinase and p42/44 MAP kinase. Aortic segments from animals on the 8.0% NaCl diet produced greater amounts of total and active transforming growth factor-beta 1 (TGF-ß1) and nitric oxide. The MEK1 inhibitor, PD-098059, and the p38 MAP kinase inhibitor, SB-203580, decreased production of these bioactive compounds to background levels. Intravenous injection of tetraethylammonium chloride (TEA) into rats on the 8.0% NaCl diet decreased the activities of p38 MAP kinase and p42/44 MAP kinase, compared with rats on the same diet and given vehicle intravenously. These findings provided direct evidence that dietary salt modulated gene expression in the arterial wall through a tetraethylammonium-sensitive mechanism and activation of the p38 and p42/44 MAP kinase pathways.
Key Words: protein kinases • transforming growth factors • nitric oxide
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